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The complete mitochondrial genome of Locastra muscosalis (Walker, 1866) was sequenced and characterized in this study, which was the first reported complete mitogenome of the genus Locastra. The mitogenome of L. muscosalis has a total length of 15,177 bp, encompassing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and an A-T rich region. Phylogenetic analysis revealed that L. muscosalis is closely associated with Orthaga euadrusalis. These data will serve as a valuable foundation for future investigations into the Epipaschiinae and Pyralidae evolutionary history.

Fish are generally classified as herbivorous, carnivorous, omnivorous, or filter-feeders according to feeding habits, including the feeding method and food content. The feeding habits of fish are reflected in their digestive organ, mainly the intestine. The intestine tract is the main site for digestion and nutritional uptake, and it is regarded as a key organ in fish nutrition. Reportedly, fish gut microbiota contributes to digestion and affect gastrointestinal tract development as well as the overall growth of the fish. The disruption of the intestinal microbiota induced by their feeding habit via diet usually affects the digestive functions of the host through disturbance in bacterial digestive enzyme production. Feeding habits determine the feed composition, which shapes the microbial communities in fish. For example, diet has been reported as a dominant cause of variation in the microbiota composition of rainbow trout. In contrast, feeding habit, which is regulated by many factors, including intrinsic and external factors, such as appetite, structure of the digestive tract, and feed palatability, is an important area of research in the intestinal microflora study. The feeding habit of fishes is one of the main factors affecting the differential colonization of fish intestinal flora. For example, the feeding habit increases the colonization of fish intestinal flora in the order omnivorous > herbivorous > carnivorous. It is also known that feeding habits influence intestinal digestion and structure. However, the influence of feeding habit on proximate composition, digestive enzyme secretion, and intestinal histomorphology is currently not well-known in fish. On the contrary, the feeding habit affects the composition and diversity of the intestinal microflora of fish. The composition and diversity of the microbiota in Carassius auratus, Ctenopharyngodon idella, Siniperca chuatsi, and Schizothorax grahami from the same environment have also not previously been studied. The present study aimed to compare and analyze the differences in the composition and diversity of the intestinal microflora of four fish species, investigating the relationship between their feeding habits and intestinal microflora as well. This study collected 12 intestine samples from each of the four fishes with different feeding habits, including omnivorous (C. auratus), herbivorous (C. idella), filter-feeder (S. chuatsi), and carnivorous (S. grahami), from the same pond. The composition and diversity of the microbial communities were determined by using high-throughput sequencing of 16S rRNA. Meanwhile, this study investigated the effects of feeding habits on the composition and diversity of the intestinal microflora of fish and predicted the potential functions of specific microflora with different nutrients. The results showed that the diversity of the intestinal microflora in fish was significantly affected by feeding habit (P < 0.05), such that higher levels occurred in the order omnivorous (C. auratus) > herbivorous (C. idella) > filter-feeder (S. grahami) > carnivorous (S. chuatsi). Proteobacteria and Firmicutes were the common dominant flora among the four fishes, although there were differences at the genera and species levels. For example, Acinetobacter and Bacteroides species were the most dominant flora in S. chuatsi and C. idella, respectively. Function prediction showed that the intestinal tract of S. chuatsi was mainly gram-negative. The disease resistance potential of C. idella was slightly higher than that of the other three fish species. Acinetobacter johnsonii, Acinetobacter lwoffii, and Pseudomonas stutzeri might help the host to digest protein, while Bacteroidetes may help the host to digest cellulose. In conclusion, feeding habit is one of the main factors affecting the differential colonization of fish intestinal flora. Analyzing the correlation between feeding habits and dominant intestinal flora as well as exploring the function of specific flora, could lay a theoretical foundation for studying the microbial effect of fish nutrition metabolism.

Path planning is a key technology for autonomous movement of inspection robot. The coal mine inspection robot has problems such as slow convergence speed and low search efficiency when planning paths using the rapidly-expanding random tree (RRT) algorithm. In order to solve the above problems, a combined force potential field guided RRT algorithm is proposed. The algorithm uses the repulsive force field in the combined force potential field to construct a dynamic step size. The coal mine inspection robot can adjust the step size near obstacles to improve the convergence speed of the algorithm. By utilizing the combined force field formed by the gravitational field in both the target node and random node directions, as well as the repulsive field generated by the nearest obstacle on the coal mine inspection robot, the generation direction of new nodes can be improved. It reduces the randomness of tree expansion and enhances the search efficiency of the algorithm. A pruning operation is performed on the paths planned based on the combined potential field guided RRT algorithm and smoothed using third-order Bessel curve. A simulation experiment is conducted in Matlab software on the path planning method of the coal mine inspection robot guided by the combined force potential field RRT algorithm. The results show that compared with the RRT algorithm and RRT* algorithm, the average path planning time of the combined potential field guided RRT algorithm in simple environments is reduced by 33.84% and 44.27%. The average path length is reduced by 15.29% and 4.42%, respectively. In complex environments, the average path planning time is reduced by 34.93% and 47.12%, and the average path length is reduced by 13.64% and 9.44%, respectively. In simulated coal mine environments, the average path planning time is reduced by 28.06% and 42.67%, and the average path length is reduced by 12.22% and 10.18%, respectively. After pruning and smoothing the path planned by the combined force potential field guided RRT algorithm, the number of turning points and angle changes in the path decrease, making the path smoother.

Collagen, as a commercial functional protein, is widely applied in food, cosmetics, biomedicine and other industries, and swim bladder is regarded as an ideal source of raw materials due to its rich collagen content. Chu’s croaker (Nibea coibor), as an economical fish that can produce high-grade swim bladder, is popularly farmed, however, its high fishmeal demand limits the development of the feed industry. Therefore, it is worth thinking about how to reduce the use of fish meal without affecting the swim bladder quality. Given that, an 8-week feeding trial was conducted to investigate the effects of fish meal partially replaced (0.0%, 5.0%, 10.0%, 15.0%, 20.0%) with composite proteins (CPs, consisted of corn protein meal and hydrolyzed feather meal) on growth, antioxidant capacity and swim bladder quality (texture and collagen deposition) of chu’s croaker. Results showed that although growth performance decrease with the increase of CPs’ replacement level, it did not compromise the swim bladder quality. Specifically, 5% - 10% CPs did not affect the growth significantly, but can improve antioxidant capacity, protein content, collagen synthesis and texture quality of swim bladder. The enhancement of swim bladder texture, including hardness, chewiness, springiness, and adhesiveness may be caused by changes in the expression of related genes, such as colga1t1, col12a1, cyp27a1, etc. These results indicated that appropriate fish meal replaced by CPs could be applied during aquaculture practice after comprehensive consideration of feed cost, growth rate and quality of swim bladder. This study provides support for the development of cost-effective feed formulations that improve the sustainability and economic viability of chu’s croaker culture.

The aggregate gradation of asphalt mixture is one of the most important factors affecting the service life of asphalt pavement. In order to study the gradation of asphalt mixture with the best comprehensive performance, this study puts forward a new method of mineral aggregate gradation optimization based on the fuzzy analytic hierarchy process and comprehensive evaluation method, aiming at the multi-level and multi-index evaluation of the road performance of asphalt mixture. First, the orthogonal test design method is applied to design nine target gradations with coarse aggregate (>4.75 mm) and fine aggregate (

Acinetobacter baumannii is a low-GC-content Gram-negative opportunistic pathogen that poses a serious global public health threat. Convenient and rapid genetic manipulation is beneficial for elucidating its pathogenic mechanisms and developing novel therapeutic methods. In this study, we report a new CRISPR-FnCpf1-based two-plasmid system for versatile and precise genome editing in A. baumannii. After identification, this new system prefers to recognize the 5′-TTN-3′ (N = A, T, C or G) and the 5′-CTV-3′ (V = A, C or G) protospacer-adjacent motif (PAM) sequence and utilize the spacer with lengths ranging from 19 to 25 nt. In direct comparison with the existing CRISPR-Cas9 system, it exhibits approximately four times the targetable range in A. baumannii. Moreover, by employing a tandem dual crRNA expression cassette, the new system can perform large-fragment deletion and simultaneous multiple gene editing, which is difficult to achieve via CRISPR-Cas9. Therefore, the new system is valuable and can greatly expand the genome editing toolbox of A. baumannii.

Currently, there is no established system for quantifying patterns of ocular ductions. This poses challenges in tracking the onset and evolution of ocular motility disorders, as current clinical methodologies rely on subjective observations of individual movements. We propose a protocol that integrates image processing, a statistical framework of summary indices, and criteria for evaluating both cross-sectional and longitudinal differences in ductions to address this methodological gap. We demonstrate that our protocol reliably transforms objective estimates of ocular rotations into normative patterns of total movement area and movement symmetry. This is a critical step towards clinical application in which our protocol could first diagnose and then track the progression and resolution of ocular motility disorders over time.

We investigated drug-induced acute neuronal electrophysiological changes using Micro-Electrode arrays (MEA) to rat primary neuronal cell cultures. Data based on 6-key MEA parameters were analyzed for plate-to-plate vehicle variability, effects of positive and negative controls, as well as data from over 100 reference drugs, mostly known to have pharmacological phenotypic and clinical outcomes. A Least Absolute Shrinkage and Selection Operator (LASSO) regression, coupled with expert evaluation helped to identify the 6-key parameters from many other MEA parameters to evaluate the drug-induced acute neuronal changes. Calculating the statistical tolerance intervals for negative-positive control effects on those 4-key parameters helped us to develop a new weighted hazard scoring system on drug-induced potential central nervous system (CNS) adverse effects (AEs). The weighted total score, integrating the effects of a drug candidate on the identified six-pivotal parameters, simply determines if the testing compound/concentration induces potential CNS AEs. Hereto, it uses four different categories of hazard scores: non-neuroactive, neuroactive, hazard, or high hazard categories. This new scoring system was successfully applied to differentiate the new compounds with or without CNS AEs, and the results were correlated with the outcome of in vivo studies in mice for one internal program. Furthermore, the Random Forest classification method was used to obtain the probability that the effect of a compound is either inhibitory or excitatory. In conclusion, this new neuronal scoring system on the cell assay is actively applied in the early de-risking of drug development and reduces the use of animals and associated costs.

Oxidative stress is a pivotal stimulating factor in neurocyte apoptosis and has been involved in the pathogenesis of Parkinson’s disease (PD). In this study, we have demonstrated that the improvement in the motor disorder of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/Pro-induced mice caused by b-Ecdysterone (b-Ecd) treatment is due to its antioxidant properties. Using open field, rotarod, and pole climbing tests, we have found that b-Ecd alleviates motor disorder in MPTP/Pro-induced mice and ultimately reduces the impairment of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra (SN). Notably, these effects of b-Ecd were not observed in Nrf2-KO mice. In addition, b-Ecd significantly reduced the formation of ROS and the level of MDA, blocked the increase of LPO, and partially reversed the GSH/GSSG ratio in MPTP/Pro-induced WT mice; however, these results were also not observed in MPTP/Pro-induced Nrf2-KO mice. Mechanistically, b-Ecd enhanced the expression levels of heme oxygenase 1 (HO-1) and GCLc, but not NQO1 (NAD(P)H quinone dehydrogenase 1) and GCLm expression. Interestingly, b-Ecd failed to increase the protein and mRNA levels of HO-1 and GCLc in Nrf2-KO mice, suggesting that b-Ecd attenuates oxidative stress through an Nrf2-dependent mechanism. Furthermore, b-Ecd promoted the expressions of PI3K/Akt phosphorylation (activity) and GSK-3b phosphorylation (inactivity). Conversely, administration of b-Ecd markedly decreased Fyn phosphorylation levels. Collectively, our findings suggest that b-Ecd focuses on Nrf2 in reducing MPTP/Pro-induced oxidative stress and subsequent motor deficits by inhibiting its nuclear export through PI3K/Akt/GSK-3b/Fyn pathway regulation. These further indicate that b-Ecd may be an absorbing therapeutic agent for PD.

Abstract Due to their intrinsic high reactivity, isolation of tin(0) complexes remains challenging. Herein, we report the synthesis of a silylene-stabilized ditin(0) complex (2) by reduction of a silylene-supported dibromostannylene (1) with 1 equivalent of magnesium (I) dimer in toluene. The structure of 2 was established by single crystal X-ray diffraction analysis. Density Functional Theory calculations revealed that complex 2 bears a Sn=Sn double bond and one lone pair of electrons on each of the Sn(0) atoms. Remarkably, complex 2 is readily methylated to give a mixed-valent methylditin cation (4), which undergoes topomerization in solution though a reversible 1,2-Me migration along a Sn=Sn bond. Computational studies showed that the three-coordinate Sn atom in 4 is the dominant electrophilic center, and allows for facile reaction with KHBBus 3 furnishing an unprecedented N-heterocyclic silylenes-stabilized distannavinylidene (5). The synthesis of 2, 4 and 5 demonstrates the exceptional ability of N-heterocyclic silylenes to stabilize low valent tin complexes.

The complete mitochondrial genome of Polythlipta liquidalis Leech, 1889 was sequenced and annotated in this study, which was the first reported complete mitogenome of the genus Polythlipta. The mitogenome of P. liquidalis is 15,305 bp in length and was predicted to encode 37 typical mitochondrial genes including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and one major non-coding A-T rich region. The maximum likelihood phylogenetic analysis based on the 13 PCGs was constructed, including P. liquidalis and 15 related Spilomelinae species, using Ostrinia furnacalis as the outgroup. The result showed that P. liquidalis is grouped with Sinomphisa plagialis. These data will serve as a molecular resource for species identification of P. liquidalis and become a valuable resource for a range of genetic, functional, evolutionary and comparative genomic studies on members of Spilomelinae.

Abstract Myopia is a major public health issue. However, interventional modalities for nonpathologic myopia are limited due to its complicated pathogenesis and the lack of precise targets. Here, we show that in guinea pig form-deprived myopia (FDM) and lens-induced myopia (LIM) models, the early initiation, phenotypic correlation, and stable maintenance of cochlin protein upregulation at the interface between retinal photoreceptors and retinal pigment epithelium (RPE) is identified by a proteomic analysis of ocular posterior pole tissues. Then, a microarray analysis reveals that cochlin upregulates the expression of the secreted frizzled-related protein 1 (SFRP1) gene in human RPE cells. Moreover, SFRP-1 elevates the intracellular Ca2+ concentration and activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling in a simian choroidal vascular endothelial cell line, and elicits vascular endothelial cell dysfunction. Furthermore, genetic knockdown of the cochlin gene and pharmacological blockade of SFRP1 abrogates the reduced choroidal blood perfusion and prevents myopia progression in the FDM model. Collectively, this study identifies a novel signaling axis that may involve cochlin in the retina, SFRP1 in the RPE, and CaMKII in choroidal vascular endothelial cells and contribute to the pathogenesis of nonpathologic myopia, implicating the potential of cochlin and SFRP1 as myopia interventional targets.

Creep is an important physical property of concrete and can lead to additional displacement, stress redistribution, and even cracking in concrete structures, inducing prestress loss of large-scale prestressed concrete structures. When an exponential algorithm is used to calculate the long-term creep of concrete, it is usually necessary to apply the continuous retardation spectra of the material. In the improved approach proposed here, the continuous retardation spectra can be obtained by the Weeks inverse Laplace transform. The CEB MC90 creep model is taken as an example to analyze the computational process, efficiency, and error of the approach. The improved approach is further applied to the ACI 209R-92, JSCE, and GL2000 concrete creep models. Through comparison with other methods, the advantages of the improved approach are illustrated, and some useful conclusions are drawn.

The widespread use of commercial feeds with high-fat content in aquaculture may lead to oxidative stress and inflammation in fish during culture, which may cause changes in fish muscle texture. Therefore, mitigating oxidative stress and inflammation during fish farming holds paramount importance in improving fish muscle quality. In this study, we investigated the effect of different dietary levels of chlorogenic acid (CGA; 0, 100, 200, 400, 800, 1600 mg/kg diet, P1–P6) in commercial diets on the muscle of blackspotted croaker (Protonibea diacanthus) through an 8-week feeding trial in open sea cages. The results showed that high dietary CGA levels (P5–P6) could significantly reduce muscle oxidative stress and inflammation (P

PurposeTo investigate the relationship between optic disc morphology, axial length, and regional distribution of retinal vessels in healthy eyes of young adults.MethodsNine hundred and two healthy eyes were enrolled in this university-based, cross-sectional study. Spectral-domain optical coherence tomography angiography was used to measure the parapapillary retinal vessel density. We automated the process of calculating optic disc tilt and rotation by using a program written in Python. Relationships between optic disc rotation, optic disc tilt, parapapillary vessel density, and other ocular parameters were analyzed using regression models.ResultsAs axial length increased, optic disc morphology became more tilted and rotated inferiorly. The superficial vessel density (SVD) and radial peripapillary capillary density (RPCD) gradually decreased in all regions except for the temporal quadrant. Increased temporal SVD (OR [95% CI] = 1.081 [1.039, 1.124], p

Abstract Monovalent group 15 cations L2Pn + (L = σ-donor ligands, Pn = N, P, As, Sb, Bi) have attracted significant experimental and theoretical interest because of their unusual electronic structures and growing synthetic potential. Herein, we describe the synthesis of a family of antimony(I) and bismuth(I) cations supported by a bis(silylene) ligand [(TBDSi2)Pn][BArF 4] (TBD = 1, 8, 10, 9-triazaboradecalin; ArF = 3,5-CF3-C6H3; Pn = Sb, (2); Bi, (3)). The structures of 2 and 3 have been unambiguously characterized spectroscopically and by X-ray diffraction analysis and DFT calculations. They feature bis-coordinated Sb and Bi atoms which exhibit two lone pairs of electrons. The reactions of 2 and 3 with methyl trifluoromethane sulfonate provide a approach for the preparation of dicationic antimony(III) and bismuth(III) methyl complexes. Compounds 2 and 3 serve as 2e donors to group 6 metals (Cr, Mo), giving rise to ionic antimony and bismuth metal carbonyl complexes 6–9.

Objective: To compare the morphological and quantitative changes in pathological myopia (PM) and the perioperative changes in posterior scleral reinforcement (PSR) using three-dimensional magnetic resonance images (3D MRI).Methods: A total of 49 patients with high myopia (HM; 98 eyes), 15 with pathological myopia (PM; 19 eyes), and 10 without high myopia (NORM; 20 eyes) were recruited between September 2019 and July 2021. The patients underwent measurements of refractive error and axial length, as well as 3D MRI of the eyeball. Python was used to analyze the 3D MRI images, calculate the vitreous volume, establish a topography of the height of the eyeball posterior surface, and calculate the rate of change in height (H). For the PM group undergoing PSR, changes in vitreous volume and the highest point of the eyeball posterior surface in four quadrants (temporal, subtemporal, nasal, and subnasal) were compared before and after PSR.Results: The vitreous volume was smaller in the NORM group compared to the HM and PM groups (p < 0.01). The PM group had a larger volume than the HM group (p < 0.01). The H for the PM group was higher than that of the NORM and HM groups (p < 0.01). After PSR in the PM group, the total vitreous volume, as well as the volume in the subnasal and supratemporal quadrants, decreased (p < 0.05). Additionally, the highest point of the eyeball’s posterior surface was generally shifted to the upper nasal side. Finally, the shape and position of the scleral band after PSR were plotted.Conclusion: 3D MRI is capable of a quantitative description of the eyeball morphology in PM and PSR. It allows for precise calculations of changes in vitreous volume and the H of the posterior surface. It also facilitates a meticulous analysis of the specific details of the scleral band following PSR.

Background: We isolated the carbapenemase-producing Enterobacteriaceae (CPE) strains from children during 2016–2021 in Shanghai, China and investigated the antimicrobial resistance, molecular and epidemiological features of these isolates. Methods: Antimicrobial susceptibility tests were performed to confirm the carbapenem resistance. Carbapenemase production was assessed by the rapid phenotypic identification of five major carbapenemases (KPC, NDM, VIM, IMP, and OXA-48), which were further confirmed by PCR amplification and sequencing. Multilocus sequence typing (MLST) was conducted for phylogenetic analyses. Results: A total of 320 CPE strains were collected from 2016 to 2021, consisting of carbapenemase-producing Klebsiella pneumoniae (CP-Kpn, 55.0%), Escherichia coli (CP-Eco, 24.5%) and Enterobacter cloacae (CP-Ecl, 20.4%) and others (2, 0.1%). NDM was the primary carbapenemase (67.6%) in children, followed by KPC(26.4%), IMP(5.3%) and OXA-48 (0.6%). The minimum inhibitory concentration (MIC) for imipenem has been increasing from 2016 to 2021. NDM and KPC isolates are high resistant while IMP strains show the lower resistant to imipenem. Invasive infection accounted for 10.7% of CPE-related infections and was mainly caused by CP-Kpn (70.6%). NDM-Kpn was detected in 51.8% of infants (70.8% of neonates), while KPC-Kpn was mainly isolated from non-infants (56.3%∼64.3%). ST11 was the primary clone (64.6%) of KPC-Kpn and presented an increasing trend from 2016 to 2021. Conclusion: NDM is widely prevalent and transfers among CPE strains in children. NDM-Kpn shows the most serious threat to infants, especially to neonates. High-risk clone of ST11 KPC-Kpn should be paid more attention and monitored continuously in children.

Abstract Fish feeding habit determines the digestive tract structure and intestinal microflora. However, the relationship between feeding habit, digestive intestinal morphology, and microbial diversity of omnivorous, herbivorous, plankton feeder, and carnivorous fish from the same environment has not been compared. This study compared the digestive enzyme activities, intestinal morphology, and intestinal microflora of omnivorous (Carassius auratus), herbivorous (Ctenopharyngodon idellus), carnivorous (Siniperca chuatsi), and plankton feeder (Schizothorax grahami) fishes and predicted the potential functions of specific microflora on different nutrients. Twelve intestine samples were collected from each of the four fishes from Dianchi Lake. The composition and diversity of microbial communities were determined by using high‐throughput sequencing of 16S rDNA. The results showed that the carnivorous fish (S. chuatsi) had higher trypsin and pancrelipase activities in the hepatopancreas and enteropeptidase in the intestine, but lower amylase activities in the intestine. The carnivorous fish intestine had more microvilli branches and complex structures than other fish species in the order carnivorous > herbivorous > plankton feeder > omnivorous. The intestinal microflora diversity was higher in the omnivorous fish and followed the order omnivorous > herbivorous > plankton feeder > carnivorous. Acinetobacter species and Bacteroides species were the most dominant flora in the carnivorous and herbivorous fishes, respectively. Acinetobacter species and Pseudomonas species might help the host to digest protein, while Bacteroidetes species may help the host to digest cellulose. Taken together, feeding habit determines the digestive enzyme activities, intestinal tissue morphology, and differential colonization of fish intestinal flora. The knowledge obtained is useful in feed formulation and feeding practices for the studied fish species.

AIM:To investigate the correlation between corneal biomechanical parameters measured by the corneal visualization Scheimpflug Technology(Corvis ST)and corneal high-order aberrations(HOAs)in children with mild to moderate myopia.METHODS:A cross-sectional study. A total of 255 pediatric patients with myopia enrolled from April to July 2021 in Tianjin Medical University Eye Hospital were continuously collected, and all the right eyes were taken for analysis. Corneal biomechanical parameters were obtained from Corvis ST. Pentacam three-dimensional anterior segment analyzer was used to measure total corneal higher-order aberrations(RMSh), third order aberrations(RMS3)and fourth order aberrations(RMS4).RESULTS:RMS3 was positively correlated with the second applanation time(A2T)(r=0.175, P=0.009)and negatively correlated with the axis length(AL)(r=-0.155, P=0.014). RMS4 was negatively correlated with the highest concavity radius(HCR)(r=-0.165, P=0.009). RMSh was negatively correlated with HCR and AL(r=-0.152, P=0.037; r=-0.175, P=0.005).CONCLUSION:There is a correlation between corneal biomechanical parameters and HOAs in children with myopia. Cornea with higher stiffness and stronger deformation resistance has smaller RMS3, RMS4 and RMSh.

PurposeTo predict the need for cycloplegic assessment, as well as refractive state under cycloplegia, based on non-cycloplegic ocular parameters in school-age children.DesignRandom cluster sampling.MethodsThe cross-sectional study was conducted from December 2018 to January 2019. Random cluster sampling was used to select 2,467 students aged 6–18 years. All participants were from primary school, middle school and high school. Visual acuity, optical biometry, intraocular pressure, accommodation lag, gaze deviation in primary position, non-cycloplegic and cycloplegic autorefraction were conducted. A binary classification model and a three-way classification model were established to predict the necessity of cycloplegia and the refractive status, respectively. A regression model was also developed to predict the refractive error using machine learning algorithms.ResultsThe accuracy of the model recognizing requirement of cycloplegia was 68.5–77.0% and the AUC was 0.762–0.833. The model for prediction of SE had performances of R^2 0.889–0.927, MSE 0.250–0.380, MAE 0.372–0.436 and r 0.943–0.963. As the prediction of refractive error status, the accuracy and F1 score was 80.3–81.7% and 0.757–0.775, respectively. There was no statistical difference between the distribution of refractive status predicted by the machine learning models and the one obtained under cycloplegic conditions in school-age students.ConclusionBased on big data acquisition and machine learning techniques, the difference before and after cycloplegia can be effectively predicted in school-age children. This study provides a theoretical basis and supporting evidence for the epidemiological study of myopia and the accurate analysis of vision screening data and optometry services.

AIM: To evaluate the prevalence of refractive errors and ocular biometry in 3573 freshman students at Tianjin Medical University for 4 consecutive years. METHODS: In this university-based, cross-sectional study, comprising 3573 students, visual acuity (VA), slit-lamp examination, non-cycloplegic auto-refraction, and ocular biometry were recorded. RESULTS: The prevalence of myopia increased annually, from 2017 to 2020 were 93.5%, 94.5%, 95.9%, and 96.2%, respectively (P=0.03), and the prevalence of high myopia was 25.7%, 26.9%, 28.6%, and 28.6%, respectively. Males tended to have a higher percentage of total astigmatism than females, with astigmatism ≥0.75 and ≥1.0 D criteria. The percentage of with-the-rule astigmatism, against-the-rule astigmatism, and oblique astigmatism was 90.3%, 5.8%, and 3.9%, respectively, with astigmatism ≥1.00 D criteria. The mean spherical equivalent, axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), corneal radius (CR), and lens position (LP) were 4.37±2.52 D, 25.28±1.24 mm, 539.49±34.98 μm, 3.31±0.34 mm, 3.47±0.21 mm, 7.8±0.28 mm, and 5.04±0.32 mm, respectively. With diopter increase in myopia, the AL became longer, CR became steeper, ACD became deeper, LT became thinner, and LP became more posterior (all P

Abstract Background Melanin is an important antioxidant in food and has been used in medicine and cosmetology. Chicken meat with high melanin content from black-boned chickens have been considered a high nutritious food with potential medicinal properties. The molecular mechanism of melanogenesis of skeletal muscle in black-boned chickens remain poorly understood. This study investigated the biological gene-metabolite associations regulating the muscle melanogenesis pathways in Wuliangshan black-boned chickens with two normal boned chicken breeds as control. Results We identified 25 differentially expressed genes and 11 transcription factors in the melanogenesis pathways. High levels of the meat flavor compounds inosine monophosphate, hypoxanthine, lysophospholipid, hydroxyoctadecadienoic acid, and nicotinamide mononucleotide were found in Wuliangshan black-boned chickens. Conclusion Integrative analysis of transcriptomics and metabolomics revealed the dual physiological functions of the PDZK1 gene, involved in pigmentation and/or melanogenesis and regulating the phospholipid signaling processes in muscle of black boned chickens.

Abstract Fisheries bycatch threatens the viability of some seabird populations and reduces fishing efficiency. Albatross bycatch in a US North Pacific tuna longline fishery has increased over the past decade and now exceeds 1000 annual captures. Seabirds interacting with this fishery reach hooks at depths up to 1 m. A branchline weight’s mass and distance from the hook affect seabird catch rates. We conducted experimental fishing to compare the commercial viability of a weighted hook relative to conventional gear with weights attached 0.75 m from the hook. We used a Bayesian random effects meta-analytic regression modelling approach to estimate pooled expected species-specific log relative risk of capture on conventional versus experimental gear. There was a significant 53% (95% HDI: − 75 to − 25%) decrease in retained species’ catch rates on experimental hooks, indicating an unacceptable economic cost, and no significant effect for discarded species. Using a Bayesian general linear mixed regression modelling approach, experimental hooks sank to 85 cm ca. 1.4 times (95% HDI: 1.37–1.48) faster than control hooks. Given their potential to reduce seabird catch rates, eliminate safety risks from bite-offs and facilitate robust compliance monitoring, it is a priority to find a weighted hook design with acceptable catch rates.

Purpose: To quantify the morphology of eyeballs with posterior staphyloma (PS) with Zernike decomposition and to explore the association between Zernike coefficients with existing PS classification.Methods: Fifty-three eyes with high myopia (HM, ≤-6.00D) and 30 with PS were included. PS was classified with traditional methods based on OCT findings. Eyeballs’ morphology was obtained with 3D MRI, from which the height map of the posterior surface was extracted. Zernike decomposition was performed to derive the coefficients of the 1st-27th items, which were compared between HM and PS eyes with the Mann-Whitney-U test. Receiver operating characteristics (ROC) analysis was used to test the effectiveness of using Zernike coefficients to discriminate PS from HM.Results: Compared to HM eyeballs, PS eyeballs had significantly increased vertical and horizontal tilt, oblique astigmatism, defocus, vertical and horizontal coma, and higher order aberrations (HOA) (all Ps < 0.05). HOA was the most effective in PS classification with an area under the ROC curve (AUROC) value of 0.977. Among the 30 PS, 19 were the wide macular type with large defocus and negative spherical aberration; 4 were the narrow macular type with positive spherical aberration; 3 were inferior PS with greater vertical tilt, and 4were peripapillary PS with larger horizontal tilt.Conclusion: PS eyes have significantly increased Zernike coefficients, and HOA is the most effective parameter to differentiate PS from HM. The geometrical meaning of the Zernike components showed great accordance with PS classification.

Background: Heart failure (HF), the final stage of cardiovascular diseases, is a clinical syndrome of cardiac structural or functional abnormalities. QiShenYiQi Dripping Pills, short for QSYQ, showed effectiveness and safety in the treatment of HF according to modern pharmacological research and clinical studies, but the mechanism remains unclear. This study aims to clarify the mechanism of QSYQ in treating heart failure through the analysis to critical biomarkers, targets and pathways.Materials and Methods: In this study, the efficacies of QSYQ in non-human primates and rodents were evaluated, and the mechanism was demonstrated by integrating network pharmacology and metabolomics analysis. Furthermore, the targets from network pharmacology and the metabolites from targeted metabolomics were jointly analyzed to screen the critical pathways.Results: In rhesus monkeys with spontaneous chronic heart failure, nasogastric administration of QSYQ for 12 weeks caused profound improvement of systolic and diastolic function as evidenced by echocardiography detection. Consistently, QSYQ administration especially with higher dose lowered the blood pressure and improved the ventricular remodeling, collagen deposition and fibrosis markedly in Spontaneous Hypertension Rats (SHR) model. Computational prediction showed that QSYQ exhibited anti-HF effects possibly through HIF-1 signaling pathway, FoxO signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway and other enriched paths. Metabolomics analysis obtained 23 significantly altered metabolites, revealing that QSYQ significantly regulated the abnormal levels of fatty acids, carnitines, organic acids pyridines, nucleosides, which were mostly involved in myocardial energy metabolism related pathways.Conclusion: Based on serum and myocardium metabolomics and network pharmacology, the present study revealed that the actions of QSYQ in treating HF depend on multi-components, multi-targets and multi-pathways.

Loperamide has been a safe and effective treatment for diarrhea for many years. However, many cases of cardiotoxicity with intentional abuse of loperamide ingestion have recently been reported. We evaluated loperamide in in vitro and in vivo cardiac safety models to understand the mechanisms for this cardiotoxicity. Loperamide slowed conduction (QRS-duration) starting at 0.3 µM [~1200-fold (×) its human Free Therapeutic Plasma Concentration; FTPC] and reduced the QT-interval and caused cardiac arrhythmias starting at 3 µM (~12,000× FTPC) in an isolated rabbit ventricular-wedge model. Loperamide also slowed conduction and elicited Type II/III A-V block in anesthetized guinea pigs at overdose exposures of 879× and 3802× FTPC. In ion-channel studies, loperamide inhibited hERG (IKr), INa, and ICa currents with IC50 values of 0.390 µM, 0.526 µM, and 4.091 µM, respectively (i.e., >1560× FTPC). Additionally, in silico trials in human ventricular action potential models based on these IC50s confirmed that loperamide has large safety margins at therapeutic exposures (≤600× FTPC) and confirmed repolarization abnormalities in the case of extreme doses of loperamide. The studies confirmed the large safety margin for the therapeutic use of loperamide but revealed that at the extreme exposure levels observed in human overdose, loperamide can cause a combination of conduction slowing and alterations in repolarization time, resulting in cardiac proarrhythmia. Loperamide’s inhibition of the INa channel and hERG-mediated IKr are the most likely basis for this cardiac electrophysiological toxicity at overdose exposures. The cardiac toxic effects of loperamide at the overdoses could be aggravated by co-medication with other drug(s) causing ion channel inhibition.

Based on the perspective of financial geography, this study analyzed the convergent mechanism of urban–rural financial imbalances under the influence of spatial spillover through the theoretical framework of spatial process, spatial action, and spatial convergence. Then, we empirically tested the spatial spillover, spatial difference, and spatial convergence of urban–rural financial imbalances in China from 1991 to 2021. We found that urban–rural financial imbalances showed significant spillover effects and heterogeneous characteristics. Spillovers based on financial radiation and exclusion were apparent during the urban financial agglomeration stage, decreasing with geographical distance, and had an essential impact on the convergence of provincial urban–rural financial imbalance. As such spillovers declined during the financial diffusion period, new spillovers at the technology and information dimensions, which were less geographically constrained, came into play and contributed to urban–rural financial convergence. The policy implications are that it is necessary to pay attention to the spatial interaction of urban–rural financial inequality, correctly use their spillover effects to achieve financial convergence, and activate new spatial spillover channels according to their spatial interaction mode changes for further urban and rural financial convergence.

Purpose: This study aimed to explore the macular structures and vascular characteristics of more myopic (MM) and contralateral eyes with highly myopic anisometropia.Methods: Comprehensive ophthalmic examinations were performed for 33 patients with highly myopic anisometropia. Macular structures (total retinal layer [TRL], ganglion cell and inner plexiform layer [GCIPL], inner nuclear layer [INL], outer retinal layer [ORL], nerve fiber layer [NFL], choroidal layer [CHL]) and vascular characteristics (superficial vascular complex density [SVD], deep vascular complex density [DVD], choriocapillaris perfusion area [CCPA]) were assessed using swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA). Macular structures and vascular characteristics of each subregion were compared to those of the Early Treatment of Diabetic Retinopathy Study (ETDRS).Results: With highly myopic anisometropia, the thicknesses of the TRL, GCIPL, INL, and ORL in MM eyes were smaller than those in contralateral eyes in at least one quadrant of the perifoveal and parafoveal circles (all p < 0.05), with no changes in the foveal and temporal quadrants of perifoveal regions (all p > 0.05). A thicker NFL (p = 0.018) was found in MM eyes than in contralateral eyes in the superior perifoveal quadrant. The CHL (all p < 0.05) in MM eyes was thinner in all regions than in the contralateral eyes according to the ETDRS. There were no statistical differences in the SVD, DVD, and CCPA of MM and contralateral eyes (all p > 0.05).Conclusion: All retinal layers, except the NFL, tended to be thinner in all subregions, except the temporal perifoveal and foveal quadrants in MM eyes, and choroidal thickness was thinned in all areas.

Introduction: Early identification of cardiac risk is essential for reducing late-stage attrition in drug development. We adapted the previously published cardiac hazard risk-scoring system using a calcium transient assay in human stem cell-derived CMs for the identification of cardiac risks recorded from the new hiPSC-CM line and investigated its predictivity and translational value based on the screening of a large number of reference and proprietary compounds.Methods: Evaluation of 55 reference drugs provided the translation of various pharmacological effects into a single hazard label (no, low, high, or very high hazard) using a Ca2+-sensitive fluorescent dye assay recorded by -by FDSS/µCell Functional Drug Screening System (Hamamatsu on hiPSC-CM line (FCDI iCell Cardiomyocytes2).Results: Application of the adapted hazard scoring system in the Ca2+ transient assay, using a second hiPS-CM line, provided comparable scoring results and predictivity of hazard, to the previously published scoring approach, with different pharmacological drug classes, as well as screening new chemical entities (NCE’s) using a single hazard label from four different scoring levels (no, low, high, or very high hazard). The scoring system results also showed minimal variability across three different lots of hiPSC-CMs, indicating good reproducibility of the cell line. The predictivity values (sensitivity and specificity) for drug-induced acute cardiac risk for QT-interval prolongation and Torsade de pointes (TdPs) were >95% and statistical modeling confirmed the prediction of proarrhythmic risk. The outcomes of the NCEs also showed consistency with findings in other well-established in vitro and in vivo cardiac risk assays.Conclusion: Evaluation of a large list of reference compounds and internal NCEs has confirmed the applicability of the adaptations made to the previously published novel scoring system for the hiPSC-CMs. The validation also established the predictivity for drug-induced cardiac risks with good translation to other established preclinical in vitro and in vivo assays, confirming the application of this novel scoring system in different stem cell-CM lines for early cardiac hazard identification.

Uveal melanoma (UM) is a highly aggressive disease. There is an urgent need to develop the metastasis prediction markers of UM. This study aims to detect the key role of PALMD in UM metastasis. Transcriptome sequencing results of 2 sets of UM metastatic samples (GSE22138 and GSE156877) were downloaded from the Gene Expression Omnibus (GEO), and 18 overlapping differentially expressed genes were screened out, including PALMD. PALMD was significantly underexpressed in metastatic UM tissue. Low expression of PALMD was associated with poor prognosis in UM patients. The decreased expression of PALMD promoted the invasion and migration of 92-1 and Mel270 cells, while the high expression of PALMD inhibited the invasion and migration of UM cells. Furthermore, the levels of matrix metallopeptidase (MMP) 2 and MMP9 increased after transfection of siRNAs specifically targeting PALMD, whereas the levels of MMP2 and MMP9 were decreased after PALMD overexpression. However, PALMD did not affect the proliferation of UM cells. In addition, ZNF263 promoted the transcription of PALMD through the putative binding sequence using the JASPAR database, luciferase reporter gene analysis and chromatin immunoprecipitation assay. In summary, the expression of PALMD regulated by ZNF263 plays an important role in UM metastasis.

Background: To investigate the correlation between the corneal biomechanical parameter stress-strain index (SSI) and axial length (AL) in moderately elongated eye (MEE) and severely elongated eye (SEE).Methods: This study included 117 eyes from 117 participants. Among them, 59 (50.4%) had MEE (AL 0.05). CCT was negatively correlated with AL (r = −0.289, p < 0.05) and ACV positively correlated with AL (r = 0.444, p < 0.001) in the MEE group. Neither CCT nor ACV was correlated with AL (p > 0.05) in the SEE group.Conclusion: Corneal biomechanical parameter SSI, which represents the stiffness of corneal tissue, was lower in the SEE group than in the MEE group. When analyzed separately, SSI was negatively correlated with AL in the MEE group, but not in the SEE group, which may provide insight into different ocular growth patterns between lower myopia and higher myopia.